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Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
Paleosols occur in the Driftless Area of southwestern Wisconsin because this area escaped direct Pleistocene glaciation, allowing long-term loess and colluvium accumulation in selected settings. The most complete known depositional sequence at Oil City, Wisconsin, contains eight lithologic units with five paleosols, all with normal remanent magnetism (i.e., <780 ka). Previous work characterized the stratigraphy, pedology, micromorphology, and clay mineralogy of the section. We investigate chemical weathering of the 8–63 µm silt fraction using X-ray diffraction (XRD) and elemental geochemistry by portable X-ray fluorescence (pXRF). Elemental ratios TiO2/CaO, Zr/Sr, and Rb/Sr generally align with the pedological evidence of weathering. Mineral ratios plagioclase/quartz and K-feldspar/quartz display greater scatter and less certainty in interpretation. The paleosols with Bt horizons have ratios indicating greater weathering than the modern soil. The most weathered paleosol is formed in the unnamed fourth loess unit stratigraphically below the Loveland Member. The stratigraphic position and higher degree of weathering support correlation of the fourth loess with the Yarmouth Geosol and Crowley’s Ridge Silt of the Middle Mississippi valley. Geochemical indices by pXRF are more consistent with established lithologic breaks than mineralogy by XRD. Our results support the use of pXRF for stratigraphic and weathering studies of Quaternary sediments.
OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.
pCO2/pH perturbation experiments were carried out under two different pCO2 levels to evaluate effects of CO2-driven ocean acidification on semi-continuous cultures of the marine diatom Skeletonema pseudocostatum CSA48. Under higher pCO2/lowered pH conditions, our results showed that CO2-driven acidification had no significant impact on growth rate, chlorophyll-a, cellular abundance, gross photosynthesis, dark respiration, particulate organic carbon and particulate organic nitrogen between CO2-treatments, suggesting that S. pseudocostatum is adapted to tolerate changes of ~0.5 units of pH under high pCO2 conditions. However, dissolved organic carbon (DOC) concentration and DOC/POC ratio were significantly higher at high pCO2, indicating that a greater partitioning of organic carbon into the DOC pool was stimulated by high CO2/low pH conditions. Total fatty acids (FAs) were significantly higher under low pCO2 conditions. The composition of FAs changed from low to high pCO2, with an increase in the concentration of saturated and a reduction of monounsaturated FAs. Polyunsaturated FAs did not show significant differences between pCO2 treatments. Our results lead to the conclusion that the balance between negative or null effect on S. pseudocostatum ecophysiology upon low pH/high pCO2 conditions constitute an important factor to be considered in order to evaluate the global effect of rising atmospheric CO2 on primary productivity in coastal ocean. We found a significant decrease in total FAs, however no indications were found for a detrimental effect of ocean acidification on the nutritional quality in terms of essential fatty acids.
Despite many advances in recent years for patients with critical paediatric and congenital cardiac disease, significant variation in outcomes remains across hospitals. Collaborative quality improvement has enhanced the quality and value of health care across specialties, partly by determining the reasons for variation and targeting strategies to reduce it. Developing an infrastructure for collaborative quality improvement in paediatric cardiac critical care holds promise for developing benchmarks of quality, to reduce preventable mortality and morbidity, optimise the long-term health of patients with critical congenital cardiovascular disease, and reduce unnecessary resource utilisation in the cardiac intensive care unit environment. The Pediatric Cardiac Critical Care Consortium (PC4) has been modelled after successful collaborative quality improvement initiatives, and is positioned to provide the data platform necessary to realise these objectives. We describe the development of PC4 including the philosophical, organisational, and infrastructural components that will facilitate collaborative quality improvement in paediatric cardiac critical care.
In this paper, a passive double-balanced mixer in SiGe HBT technology is presented. Owing to lack of suitable passive mixing elements in the technology, the mixing elements are formed by diode-connected HBTs. The mixer uses lumped element Marchand baluns on both the local oscillator (LO) and the radio frequency (RF) port. A break out of the Marchand balun is measured. This demonstrates good phase and magnitude match of 0.7° and 0.11 dB, respectively. The Marchand baluns are broadband with a measured 3 dB bandwidth of 6.4 GHz, while still having a magnitude imbalance better than 0.4 dB and a phase imbalance better than 5°. Unfortunately with a rather high loss of 2.5 dB, mainly due to the low Q-factor of the inductors used. The mixer is optimized for use in doppler radars and is highly linear with a 1 dB compression point above 12 dBm IIP2 of 66 dBm. The conversion gain at the center frequency of 8.5 GHz is −9.8 dB at an LO drive level of 15 dBm. The whole mixer is very broadband with 3 dB bandwidth from 7 to 12 GHz covering the entire X-band. The LO–IF, RF–IF, and RF–LO isolation is better than 46, 36, and 36 dB, respectively, in the entire band of operation.
Loess has been recognized on the glacial land surface of the Green Bay Lobe for over 100 yr, but no systematic explanation of the source of the loess has been advanced. Intriguingly, the loess on the Green Bay Lobe land surface is thicker than predicted by regional thinning trends from the Mississippi Valley and is geographically separated from much loess of southwest Wisconsin by a sandy region devoid of loess. Mapping based on soil survey interpretation indicates that the loess occurs above an escarpment marking the eastern end of the sandy loess-free region. Particle size fining trends demonstrate that the loess was transported by northwesterly winds. Clay mineralogy of the Green Bay Lobe loess is distinctly different than glaciogenic sediments and matches loess of the Mississippi Valley, indicating a regional source and long distance transport of the loess. We propose the loess was transported from the regional source along a surface of transport produced by migration of eolian sand through low-relief landscapes including the glacial Lake Wisconsin basin. Eolian sand migration caused repeated entrainment of dust leading to east-southeastward transport. The loess accumulated above an escarpment that limited sand mobility and re-entrainment of loess beyond this topographic barrier.